Analytical test strip with capillary sample-receiving chambers separated by a physical barrier island

ABSTRACT

An analytical test strip for the determination of an analyte (such as glucose and/or hematocrit) in a bodily fluid sample (such as a whole blood sample) includes a first capillary sample-receiving chamber, a second capillary sample-receiving chamber, and a physical barrier island disposed between the first and second capillary sample-receiving chambers. Moreover, the physical island barrier is disposed such that bodily fluid sample flow between the first capillary sample-receiving chamber and the second capillary sample-receiving chamber is prevented during use of the analytical test strip.

CROSS-REFERENCE TO RELATED APPLICATIONS

This DIVISIONAL application claims the benefits of priority under 35 USC§§120 and 121 from prior filed U.S. application Ser. No. 13/529,901filed on Jun. 21, 2012, allowed, in which prior filed application isincorporated by reference in its entirety into this application.

BACKGROUND OF THE INVENTION

Field of the Invention

The present invention relates, in general, to medical devices and, inparticular, to analytical test strips and related methods.

Description of Related Art

The determination (e.g., detection and/or concentration measurement) ofan analyte in a fluid sample and/or the determination of acharacteristic of a fluid sample (such as haematocrit) are of particularinterest in the medical field. For example, it can be desirable todetermine glucose, ketone bodies, cholesterol, lipoproteins,triglycerides, acetaminophen and/or HbA1c concentrations in a sample ofa bodily fluid such as urine, blood, plasma or interstitial fluid. Suchdeterminations can be achieved using analytical test strips, based on,for example, visual, photometric or electrochemical techniques.Conventional electrochemical-based analytical test strips are describedin, for example, U.S. Pat. Nos. 5,708,247, and 6,284,125, each of whichis hereby incorporated in full by reference.

BRIEF DESCRIPTION OF THE DRAWINGS

The accompanying drawings, which are incorporated herein and constitutepart of this specification, illustrate presently preferred embodimentsof the invention, and, together with the general description given aboveand the detailed description given below, serve to explain features ofthe invention, in which:

FIG. 1 is a simplified exploded view of an electrochemical-basedanalytical test strip according to an embodiment of the presentinvention;

FIG. 2 is a sequence of simplified top views of the various layers ofthe electrochemical-based analytical test strip of FIG. 1;

FIG. 3 is a simplified top view representation of the substrate layerand spacer layer of the electrochemical-based analytical test strip ofFIG. 1;

FIG. 4 is a simplified side view of a portion of theelectrochemical-based analytical test strip of FIG. 1 that, for clarity,omits the reagent layer, patterned insulation layer and patternedconductor layer thereof;

FIG. 5 is a simplified top view of the electrochemical-based analyticaltest strip of FIG. 1 depicting various components thereof; and

FIG. 6 is a flow diagram depicting stages in a method for determining ananalyte in a bodily fluid sample according to an embodiment of thepresent invention.

DETAILED DESCRIPTION OF ILLUSTRATIVE EMBODIMENTS

The following detailed description should be read with reference to thedrawings, in which like elements in different drawings are identicallynumbered. The drawings, which are not necessarily to scale, depictexemplary embodiments for the purpose of explanation only and are notintended to limit the scope of the invention. The detailed descriptionillustrates by way of example, not by way of limitation, the principlesof the invention. This description will clearly enable one skilled inthe art to make and use the invention, and describes severalembodiments, adaptations, variations, alternatives and uses of theinvention, including what is presently believed to be the best mode ofcarrying out the invention.

As used herein, the terms “about” or “approximately” for any numericalvalues or ranges indicate a suitable dimensional tolerance that allowsthe part or collection of components to function for its intendedpurpose as described herein.

In general, analytical test strips (e.g., electrochemical-basedanalytical test strips) for the determination of an analyte (such asglucose and/or hematocrit) in a bodily fluid sample (for example, wholeblood) according to embodiments of the present invention include a firstcapillary sample-receiving chamber, a second capillary sample-receivingchamber, and a physical barrier island disposed between the first andsecond capillary sample-receiving chambers. Moreover, the physicalisland barrier is disposed such that bodily fluid sample flow betweenthe first capillary sample-receiving chamber and the second capillarysample-receiving chamber is prevented during use of the analytical teststrip.

Analytical test strips according to embodiments of the present inventionare beneficial in that, for example, the physical barrier island servesto maintain the fluidic integrity of the first and second capillarysample-receiving chambers while also being easily manufactured. Suchfluidic integrity beneficially prevents mixing of reagents and reactionbyproducts between the first and second capillary sample-receivingchambers that can lead to inaccuracies in analyte or bodily fluid samplecharacteristic determination. Moreover, since the physical barrierisland can be relatively small, sample application openings for thefirst and second capillary sample application chambers can be juxtaposedclose to one another (for example, separated by a distance ofapproximately 250 microns that can be operatively bridged by a wholeblood sample of approximately 1 micro-liter) such that the singleapplication of a bodily fluid sample bridges both sample applicationopenings and fills both the first and the second capillarysample-receiving chambers. Furthermore, the physical barrier island canbe manufactured in a relatively simple and inexpensive manner usingmanufacturing conventional techniques.

FIG. 1 is a simplified exploded view of an electrochemical-basedanalytical test strip 100 according to an embodiment of the presentinvention. FIG. 2 is a sequence of simplified top views of the variouslayers of electrochemical-based analytical test strip 100. FIG. 3 is asimplified top view representation of the substrate layer and spacerlayer (a portion of which is configured as a physical barrier island) ofelectrochemical-based analytical test strip 100. FIG. 4 is a simplifiedside view of a portion of electrochemical-based analytical test strip100 that, for clarity, omits the reagent layer, patterned insulationlayer and patterned conductor layer thereof. FIG. 5 is a simplified topview of electrochemical-based analytical test strip 100 depictingvarious components, including the electrodes, thereof.

Referring to FIGS. 1-5, electrochemical-based analytical test strip 100for the determination of an analyte (such as glucose) in a bodily fluidsample (for example, a whole blood sample) includes anelectrically-insulating substrate layer 120, a patterned conductor layer140, a patterned insulation layer 160 with electrode exposure window 180therein, an enzymatic reagent layer 200, a patterned spacer layer 220that includes a physical barrier island 220 a, a hydrophilic layer 240,and a top layer 260.

The disposition and alignment of electrically-insulating substrate layer120, patterned conductor layer 140 (which a variety of electrodes 140 a,see FIG. 5 in particular), patterned insulation layer 160, enzymaticreagent layer 200, patterned spacer layer 220 (and physical barrierisland 220 a thereof), hydrophilic layer 240 and top layer 260 ofelectrochemical-based analytical test strip 100 are such that a firstcapillary sample-receiving chamber 262 and a second capillarysample-receiving chamber 264 of electrochemical-based analytical teststrip 100 are defined.

Physical barrier island 220 a is disposed between first capillarysample-receiving chamber 262 and second capillary sample-receivingchamber 264 such that fluid flow therebetween during use ofelectrochemical-based analytical test strip 100 is prevented.

It should be noted that in the embodiments depicted in FIGS. 1-5 thephysical barrier island is disposed essentially parallel to the primaryflow direction of a bodily fluid that is filling the first and secondcapillary sample-receiving chambers. The physical barrier island,therefore, does not prevent bodily fluid from filling the first andsecond capillary sample-receiving chambers but rather prevents bodilyfluid that has entered either of the capillary sample-receiving chambersfrom entering the other capillary sample-receiving chamber.

In the perspective of FIG. 4, first and second capillarysample-receiving chambers 262 and 264 have a height of approximately 100μm, a width in the range of approximately 1.45 mm to 1.65 mm, and apitch of approximately 2.55 mm. The abrupt change in vertical dimensionthat creates the stop junctions is an additional height of approximately100 μm.

Patterned conductor layer 140, including electrodes 140 a, ofelectrochemical-based analytical test strip 100 can be formed of anysuitable conductive material including, for example, gold, palladium,platinum, indium, titanium-palladium alloys and electrically conductingcarbon-based materials including carbon inks. Referring in particular toFIG. 5, electrode exposure window 180 of patterned insulation layer 160exposes three electrodes 140 a in the lower portion of the FIG. (forexample, a counter/reference electrode and first and second workingelectrodes) configured for the electrochemical determination of ananalyte (glucose) in a bodily fluid sample (whole blood). Electrodeexposure window 180 also exposes two electrodes (in the upper portion ofthe FIG.) configured for the determination of haematocrit in wholeblood. The determination of haematocrit using electrodes of ananalytical test strip is described in, for example, U.S. PatentApplication Nos. 61/581,100; 61/581,097; 61/581,089; 61/530,795 and61/530,808, each of which is hereby incorporated in full by reference.

During use, a bodily fluid sample is applied to electrochemical-basedanalytical test strip 100 and fills both the first and second capillarysample-receiving chambers by capillary action and, thereby, operativelycontacts the electrodes disposed in the first and second capillarysample-receiving chambers. Referring to FIG. 3 in particular, firstcapillary sample-receiving chamber 262 has at least one sampleapplication opening (namely two openings 270 a and 270 b) and secondcapillary sample-receiving chamber 264 has at least one sampleapplication opening (namely, two sample application openings 272 a and272 b). Each of the first and second capillary sample-receiving chambersare configured such that a sample can be applied and fill both of thecapillary sample-receiving chambers from either the left-hand side(using sample application openings 270 a and 272 a) of the analyticaltest strip or the right-hand-side (using sample application openings 270b and 272 b). In either circumstance, the sample application opening ofthe first capillary sample-receiving chamber and the sample applicationopening of the second capillary sample-receiving chamber are juxtaposedsuch that a single bodily fluid sample can be simultaneously appliedthereto.

In the embodiments of FIGS. 1-5, physical barrier island 220 a has awidth that is less than the width of the electrochemical-basedanalytical test strip (see FIG. 3 in particular, where “width” in thiscontext refers to a horizontal dimension in the perspective of FIG. 3).In other words, although physical barrier island 220 a is disposedlongitudinally along the first and second capillary sample-receivingchambers, the physical barrier island does not extend to the lateraledges of the electrochemical-based analytical test strip.

The aforementioned lesser width and disposition of physical barrierisland 220 a serves define a first shared sample entry chamber 274 atthe first sample application opening 270 a of the first capillarysample-receiving chamber 262 and the first sample application opening272 a of the second capillary sample-receiving chamber 264, and a secondshared sample entry chamber 276 at the second sample application opening270 b of the first capillary sample-receiving chamber 262 and the secondsample application opening 272 b of the second capillarysample-receiving chamber 264. For clarity, the area of first and secondshared sample entry chambers 274 and 276 is shown with cross-hatching inFIG. 3.

First shared sample entry chamber 274 and second shared sample entrychamber 276 are beneficial in that, for example, an applied bodily fluidsample can more easily overcome surface tension forces to fill a such asingle shared sample entry chamber (and subsequently fill the first andsecond capillary sample-receiving chambers), as opposed to overcomingthe surface tension of two separate sample entry chambers. In addition,the width (in this context the vertical direction of FIG. 3) of eitherof the first and second shared sample entry chambers is greater than thewidth of either of the first or second sample application openings andis also greater than the sum of the widths of both of the first sampleapplication openings or the sum of the widths of both of the secondsample application openings. Therefore, a user can more easily apply abodily fluid sample to such relatively large width in comparison to thewidth of a sample application opening of a capillary sample-receivingchamber.

Electrically-insulating substrate layer 120 can be any suitableelectrically-insulating substrate layer known to one skilled in the artincluding, for example, a nylon substrate, polycarbonate substrate, apolyimide substrate, a polyvinyl chloride substrate, a polyethylenesubstrate, a polypropylene substrate, a glycolated polyester (PETG)substrate, or a polyester substrate. The electrically-insulatingsubstrate layer can have any suitable dimensions including, for example,a width dimension of about 5 mm, a length dimension of about 27 mm and athickness dimension of about 0.35 mm.

Electrically-insulating substrate layer 120 provides structure to thestrip for ease of handling and also serves as a base for the application(e.g., printing or deposition) of subsequent layers (e.g., a patternedconductor layer). It should be noted that patterned conductor layersemployed in analytical test strips according to embodiments of thepresent invention can take any suitable shape and be formed of anysuitable materials including, for example, metal materials andconductive carbon materials.

Patterned insulation layer 160 can be formed, for example, from a screenprintable insulating ink. Such a screen printable insulating ink iscommercially available from Ercon of Wareham, Mass. U.S.A. under thename “Insulayer.”

Patterned spacer layer 220 can be formed, for example, from ascreen-printable pressure sensitive adhesive commercially available fromApollo Adhesives, Tamworth, Staffordshire, or other suitable materialssuch as, for example, polyester and polypropylene. The thickness ofpatterned spacer layer 220 can be, for example 75 μm. In the embodimentof FIGS. 1 through 5, patterned spacer layer 220 defines an outer wallof the first and second capillary sample-receiving chamber 280.

Hydrophilic layer 240 can be, for example, a clear film with hydrophilicproperties that promote wetting and filling of electrochemical-basedanalytical test strip 100 by a fluid sample (e.g., a whole bloodsample). Such clear films are commercially available from, for example,3M of Minneapolis, Minn. U.S.A. and Coveme (San Lazzaro di Savena,Italy). Hydrophilic layer 240 can be, for example, a polyester filmcoated with a surfactant that provides a hydrophilic contact angle ofless than 10 degrees. Hydrophilic layer 240 can also be a polypropylenefilm coated with a surfactant or other surface treatment, e.g., a MESAcoating. Hydrophilic layer 240 can have a thickness, for example, ofapproximately 100 μm.

Enzymatic reagent layer 200 can include any suitable enzymatic reagents,with the selection of enzymatic reagents being dependent on the analyteto be determined. For example, if glucose is to be determined in a bloodsample, enzymatic reagent layer 200 can include a glucose oxidase orglucose dehydrogenase along with other components necessary forfunctional operation. Enzymatic reagent layer 200 can include, forexample, glucose oxidase, tri-sodium citrate, citric acid, polyvinylalcohol, hydroxyl ethyl cellulose, potassium ferrocyanide, antifoam,cabosil, PVPVA, and water. Further details regarding enzymatic reagentlayers, and electrochemical-based analytical test strips in general, arein U.S. Pat. Nos. 6,241,862 and 6,733,655, the contents of which arehereby fully incorporated by reference.

Top layer 260 can be formed of any suitable mater including, forexample, polyester materials, polypropylene materials, and other plasticmaterials. Top layer 260 can have a thickness, for example ofapproximately 50 μm.

Electrochemical-based analytical test strip 100 can be manufactured, forexample, by the sequential aligned formation of patterned conductorlayer 140, patterned insulation layer 160, enzymatic reagent layer 200,patterned spacer layer 220, hydrophilic layer 240 and top layer 260 ontoelectrically-insulating substrate layer 120. Any suitable techniquesknown to one skilled in the art can be used to accomplish suchsequential aligned formation, including, for example, screen printing,photolithography, photogravure, chemical vapour deposition and tapelamination techniques.

FIG. 6 is a flow diagram depicting stages in a method 600 fordetermining an analyte (such as glucose) in a bodily fluid sample (forexample, a whole blood sample) and/or a characteristics of the bodilyfluid sample (e.g., hematocrit) according to an embodiment of thepresent invention. Method 600 includes (see step 610 of FIG. 6) applyinga bodily fluid sample to an analytical test strip such that the appliedbodily fluid sample fills a first capillary sample-receiving chamber anda second capillary sample-receiving chamber of the analytical test stripand is prevented from flowing between the first capillarysample-receiving chamber and the second capillary sample-receivingchamber by a physical barrier island of the analytical test strip.

Method 600 also includes measuring a first response of the analyticaltest strip (for example an electrochemical response from electrodes inthe first capillary sample-receiving chamber) and determining an analytein the bodily fluid sample is determined based on the first measuredelectrochemical response (see steps 620 and 630 of FIG. 6).

In steps 640 and 650 of method 600 also includes, measuring a secondresponse of the analytical test strip (for example, an electricalresponse from electrodes in the second capillary sample-receivingchamber) and determining a characteristic of the bodily fluid samplebased on the second measured response. The measuring and determinationsteps described above can, if desired, by performed using a suitableassociated meter and measurement steps 620 and 630 can be performed inany suitable sequence or in an overlapping manner.

Once apprised of the present disclosure, one skilled in the art willrecognize that method 600 can be readily modified to incorporate any ofthe techniques, benefits and characteristics of analytical test stripsaccording to embodiments of the present invention and described herein.

While preferred embodiments of the present invention have been shown anddescribed herein, it will be obvious to those skilled in the art thatsuch embodiments are provided by way of example only. Numerousvariations, changes, and substitutions will now occur to those skilledin the art without departing from the invention. It should be understoodthat various alternatives to the embodiments of the invention describedherein may be employed in practicing the invention. It is intended thatthe following claims define the scope of the invention and that devicesand methods within the scope of these claims and their equivalents becovered thereby.

What is claimed is:
 1. A method for determining an analyte in a bodilyfluid sample, the method comprising: providing an analytical test strip,the analytical test strip having: an electrically insulating substratelayer; at least one reference electrode and a plurality of workingelectrodes, all of which are disposed on the electrically insulatingsubstrate layer; and an enzymatic reagent layer disposed over at leastone of, but not all of the working electrodes; applying a bodily fluidsample to the analytical test strip such that the applied bodily fluidsample fills a first capillary sample-receiving chamber and a secondcapillary sample-receiving chamber of the analytical test strip and isprevented from flowing between the first capillary sample-receivingchamber and the second capillary sample-receiving chamber by a physicalbarrier island; measuring at least a first response of the analyticaltest strip; and determining the analyte based on the first measuredelectrochemical response.
 2. The method of claim 1 further including:measuring a second response of the analytical test strip that isdependent on bodily fluid sample in the second capillarysample-receiving chamber; and determining a characteristic of the bodilyfluid sample based on the second measured response.
 3. The method ofclaim 1 wherein the bodily fluid sample is whole blood.
 4. The method ofclaim 1 wherein the analyte is glucose.
 5. The method of claim 1 whereinthe applying step includes applying a single bodily fluid sample to asample application opening of the first capillary sample-receivingchamber a sample application opening of the second capillarysample-receiving chamber, and wherein the sample application opening ofthe first capillary sample-receiving chamber and the sample applicationopening of the second sample-receiving chamber are juxtaposed such thatthe single bodily fluid sample can be simultaneously applied thereto. 6.The method of claim 5 wherein the physical barrier island extendslongitudinally along the first capillary sample-receiving chamber andthe second capillary sample-receiving chamber from the sampleapplication opening of the first capillary sample receiving chamber andthe sample application opening of the second capillary sample-receivingchamber.
 7. The method of claim 6 wherein the physical barrier island isdisposed such that: a first shared sample entry chamber is defined atthe first sample application opening of the first capillarysample-receiving chamber and the first sample application opening of thesecond capillary sample-receiving chamber and a second shared sampleentry chamber is defined at the second sample application opening of thefirst capillary sample-receiving chamber and the second sampleapplication opening of the second capillary sample-receiving chamber. 8.The method of claim 7 wherein a width of the first shared sample entrychamber is greater than the sum of widths of the first sampleapplication opening of the first capillary sample-receiving chamber andthe first sample application opening of the second capillary-samplereceiving chamber, and wherein a width of the second shared sample entrychamber is greater than the sum of widths of the second sampleapplication opening of the first capillary sample-receiving chamber andthe second sample application opening of the second capillary-samplereceiving chamber.
 9. The method of claim 1 wherein the analytical teststrip is configured as an electrochemical-based analytical test strip.